Flavonol derivatives containing pyrazole oxime ether: design, synthesis, and anti-TMV activity

Abstract

A series of flavonol derivatives containing pyrazole oxime ether moieties were designed and synthesized. In vivo antiviral assays revealed that some compounds exhibited remarkable inhibitory effects against tobacco mosaic virus (TMV). Among them, Both the curative activity (EC₅₀ = 88.9 μg/mL) and protective activity (EC₅₀ = 107.5 μg/mL) of H13 were shown to be significantly superior to those of the reference agent ningnanmycin (NNM) (208.4 μg/mL and 190.1 μg/mL, respectively). Mechanistic studies indicated that both microscale thermophoresis (MST) experiments and molecular docking results demonstrate that H13 exhibits stronger binding capacity and affinity for the tobacco mosaic virus coat protein (TMV-CP) than NNM. Density functional theory (DFT) calculations further revealed higher chemical reactivity of H13. Additionally, H13 treatment significantly enhanced chlorophyll content in tobacco leaves, improving photosynthetic efficiency, while reduced malondialdehyde (MDA) levels indicated strengthened disease resistance. ADME property prediction suggested no significant ocular toxicity or hERG inhibition risk for H13. Plant experiments confirmed that H13 caused no adverse effects on tobacco seed germination or leaf growth.

Keywords: Anti-TMV; Flavonol; Mechanism of action; Pyrazole oxime ether.